Infection is a common and frequently very serious complication associated with medical implants. Man-made materials, including those used to fabricate ventricular assist devices (VADs), compromise the body's ability to fight infection in tw ways. First, by breaching skin with transcutaneous cannulae and drivelines, and second, by eliciting a foreign body reaction which results in scarring near the implant surface that creates an environment where bacteria can thrive outside the reach of the body's immune system. Currently available infection resistant materials typically rely on the release of antimicrobial substances. Though effective over the short-term, the released drugs can compromise normal healing and exacerbate the problem of isolating the implant surface from the body's immune defenses. Ension proposes development of an infection resistant surface designed to promote normal healing for application to the transcutaneous drivelines of ventricular assist devices. The proposed surface will incorporate a three-pronged approach to infection resistance; a low adhesion surface designed to prevent or hinder the attachment of microbes, controlled release of antimicrobial agents, and a natural collagen surface that promotes tissue integration. The innovation of the surface lies in going beyond the partial solution of acute antimicrobial release (such as the silver-impregnated gauze typically used in VAD transcutaneous driveline applications) to an engineered surface that also promotes optimal healing response of the adjacent tissue. The normal healing response near the surface generates tissue devoid of scarring and chronic inflammation, assuring a normal immune response and thus improving long-term infection resistance. Preliminary in vitro testing using prototype surfaces demonstrated that the proposed surface facilitates fibroblast adhesion (a part of normal healing), resists attachment of bacteria, and avoids causing toxicity that would hinder normal healing. The proposed Fast Track project will refine the most promising prototype surface and apply it to polyurethane substrate material (Phase I Specific Aim 1), fabricate and test implants treated with the optimized surface for biocompatibility in mice (Phase I Specific Aims 2 and 3), and perform detailed in vivo evaluation of infection resistance in pigs (Phase II). The Phase II in vivo testing will include groups of pigs implanted with bacterial challenge at implant, with periodic bacterial challenges following implant, and unchallenged controls (Phase II Specific Aim 2). Fluorescence labeling and confocal microscopy will be used to determine the types and numbers of cells at or near the implant surface and their spatial distribution (Phase II Specific Aim 3). These methods also allow detection of fibrin and collagen in the same tissue samples. The data obtained will be compared both to controls and to established data observed during normal healing. The surface is expected to show improvement over untreated controls with respect to healing response, bacterial adhesion, local infection and systemic signs of infection. Successful completion of the Fast Track project plan will result in a surface ready for qualification testing, regulatory approval, and subsequent commercialization.